Healthy respiratory microbiome: an innovative project within the first birth cohort in Angola

Childhood pneumonia remains the major infant killer worldwide and displays a particularly devastating effect in sub-Saharan Africa despite the implementation and scaling-up of preventive programs and early management against paediatric pneumonia in developing countries. Studying the human microbiome and its positive effects in health may be one of the answers needed to tackle paediatric mortality caused by infectious diseases. This collaborative project between Portuguese and Angolan institutions aims to establish a birth cohort in the study area covered by CISA (Centro de Investigação em Saúde de Angola) in order to determine the healthy respiratory microbiome that could be the target for innovative preventive measures. Moreover the birth cohort will be a research platform enabling the attraction of competitive funds, promoting translational research and creating opportunities to train Angolan researchers.publishersversionpublishe

Inorganic phosphate modulates the expression of the NaPi-2a transporter in the trans -golgi network and the interaction with PIST in the proximal tubule

Inorganic phosphate (Pi) homeostasis is maintained by the tight regulation of renal Pi excretion versus reabsorption rates that are in turn modulated by adjusting the number of Pi transporters (mainly NaPi-2a) in the proximal tubules. In response to some hormones and a high dietary Pi content, NaPi-2a is endocytosed and degraded in the lysosomes; however, we show here that some NaPi-2amolecules are targeted to the trans-Golgi network (TGN) during the endocytosis. In the TGN, NaPi-2a interacts with PIST (PDZ-domain protein interacting specifically with TC10), a TGN-resident PDZ-domain-containing protein. The extension of the interaction is proportional to the expression of NaPi-2a in the TGN, and, consistent with that, it is increased with a high Pi diet. When overexpressed in opossum kidney (OK) cells, PIST retains NaPi-2a in the TGN and inhibits Na-dependent Pi transport. Overexpression of PIST also prevents the adaptation of OK cells to a low Pi culture medium. Our data supports the view that NaPi-2a is subjected to retrograde trafficking from the plasma membrane to the TGN using one of the machineries involved in endosomal transport and explains the reported expression of NaPi-2a in the TGN

“Tu barrio me suena”, un proyecto de innovación y colaboración entre las etapas escolares y la comunidad educativa.

Se trata de un análisis sobre la transición de los alumnos de Primaria a la etapa secundaria, así como de la participación del entorno exterior y del resto de agentes educativos en el proceso de aprendizaje de los alumnos, a través de la implementación de un proyecto de innovación educativa, llamado "Tu barrio me suena

Analysis and control of the intermediate memory states of RRAM devices by means of admittance parameters

Producción CientíficaA thorough study of the admittance of TiN/Ti/HfO2/W bipolar resistive memories [resistance random access memory (RRAM)] was carried out under different bias conditions and in a wide range of ac signal frequencies. We demonstrate that a continuum of intermediate states can be obtained by applying appropriate dc bias waveforms. Cumulative writing and erasing admittance cycles were performed by applying triangular voltage waveform of increasing amplitude. The influence of the initial conditions on the variation of the real (conductance) and imaginary (susceptance) components of the admittance is described. An accurate control of the memory state is achieved both in terms of the conductance and the susceptance by means of an adequate selection of the voltage values previously applied. A method to obtain three-dimensional voltage-conductance-susceptance state-plots is described in detail. Memory maps of admittance parameters as a function of the programming voltage are made by sensing the memory state at 0 V, without static power consumption. The multilevel nature of RRAM devices and their suitability for neuromorphic computation are demonstrated.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (grants TEC2014-52152-C3-3-R and TEC2014- 52152-C3-1-R

Aging-associated renal disease in mice is fructokinase dependent

Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (<5%) fructose content. At the end of 2 yr, wild-type mice showed elevations in systolic blood pressure, mild albuminuria, and glomerular changes with mesangial matrix expansion, variable mesangiolysis, and segmental thrombi. The renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration. aging is associated with the development of glomerulosclerosis and tubulointerstitial disease in humans and rodents (12, 23, 35). Interestingly, aging-associated renal injury can vary greatly, and some individuals may show minimal reduction in kidney function and relatively preserved kidney histology with age. This raises the possibility that some of the “normal” deterioration in renal function during the aging process observed in Western cultures may be subtle renal injury driven by diet or other mechanisms. The ingestion of sugar has been associated with albuminuria in humans (3, 4, 31). Sugar contains fructose and glucose, and evidence suggests that the fructose component may be responsible for the renal injury. Specifically, fructose is metabolized in the proximal tubule by fructokinase, and this results in transient ATP depletion with the generation of oxidative stress and inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1) (5). The administration of fructose to rats results in modest proximal tubular injury, and has also been shown to accelerate preexistent kidney disease (9, 26). Fructose metabolism also results in the generation of uric acid, and this is associated with the development of afferent arteriolar disease with loss of autoregulation, resulting in glomerular hypertension (29, 30). While most studies have focused on dietary fructose, fructose can also be generated in the kidney and liver by the aldose reductase-sorbitol dehydrogenase polyol pathway, and modest fructose levels can be detected even in fasting animals (13, 21). Indeed, fructose can be generated in the kidney in diabetes or with dehydration, and in both situations may lead to local renal damage (20, 28). We hypothesized that some of the renal damage associated with aging could be due to fructose-dependent renal injury, even in the absence of dietary fructose. To investigate this hypothesis, we studied aging wild-type mice and aging mice that could not metabolize fructose via the fructokinase-dependent pathway [fructokinase knockout, also known as ketohexokinase knockout (KHK-A/C KO mice)]. KHK-A/C KO mice have a normal phenotype when young (6), but have not been examined in the aging state

Mejorando la IOT con el Dispositivo Airtraq®. Descripción de la maniobra "KET"

La vía aérea difícil (VAD) es la primera causa de morbi-mortalidad anestésica. Representa el 50% de las complicaciones severas no fatales y el 30% de las muertes de causa anestésica. Uno de cada tres casos de VAD son imprevistos. Dentro del algoritmo de manejo de la VAD no conocida cada vez toman más importancia los dispositivos ópticos como el Airtraq®, ya que mejoran la visibilidad de la glotis respecto al laringoscopio convencional. El Airtraq® es un dispositivo de fácil utilización y aprendizaje, que posee pocas limitaciones: apertura bucal < 20 mm, macroglosia, distancia tiromentoniana reducida, etc... Presentamos un caso clínico en el que explicamos cómo resolvemos en nuestro hospital aquellas situaciones en las que no es posible avanzar el tubo endotraqueal (TET) usando el laringoscopio Airtraq®

A thorough investigation of the switching dynamics of TiN/Ti/10 nm-HfO2/W resistive memories

Producción CientíficaThe switching dynamics of TiN/Ti/HfO2/W-based resistive memories is investigated. The analysis consisted in the systematic application of voltage sweeps with different ramp rates and temperatures. The obtained results give clear insight into the role played by transient and thermal effects on the device operation. Both kinetic Monte Carlo simulations and a compact modeling approach based on the Dynamic Memdiode Model are considered in this work with the aim of assessing, in terms of their respective scopes, the nature of the physical processes that characterize the formation and rupture of the filamentary conducting channel spanning the oxide film. As a result of this study, a better understanding of the different facets of the resistive switching dynamics is achieved. It is shown that the temperature and, mainly, the applied electric field, control the switching mechanism of our devices. The Dynamic Memdiode Model, being a behavioral analytic approach, is shown to be particularly suitable for reproducing the conduction characteristics of our devices using a single set of parameters for the different operation regimes.Ministerio de Ciencia e Innovación de España - FEDER [PID2022-139586NB-C41, PID2022-139586NB-C42, PID2022-139586NB-C43, PID2022-139586NB-C44]Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía [B-TIC-624-UGR20]Consejo Superior de Investigaciones Científicas (CSIC)- FEDER [20225AT012]Ramón y Cajal grant number RYC2020-030150-IEuropean project MEMQuD (code 20FUN06) which has received funding from the EMPIR programme co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation programme

Variability and power enhancement of current controlled resistive switching devices

Producción CientíficaIn this work, the unipolar resistive switching behaviour of Ni/HfO2/Si(n+) devices is studied. The structures are characterized using both current and voltage sweeps, with the device resistance and its cycle-to-cycle variability being analysed in each case. Experimental measurements indicate a clear improvement on resistance states stability when using current sweeps to induce both set and reset processes. Moreover, it has been found that using current to induce these transitions is more efficient than using voltage sweeps, as seen when analysing the device power consumption. The same results are obtained for devices with a Ni top electrode and a bilayer or pentalayer of HfO2/Al2O3 as dielectric. Finally, kinetic Monte Carlo and compact modelling simulation studies are performed to shed light on the experimental results.Junta de Andalucía - FEDER (B-TIC-624-UGR20)Consejo Superior de Investigaciones Científicas (CSIC) (project 20225AT012)Ramón y Cajal (grant RYC2020-030150-I

Multi-scale, whole-system models of liver metabolic adaptation to fat and sugar in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue associated with high fat, high sugar diets. However, the molecular mechanisms mediating NAFLD pathogenesis are only partially understood. Here we adopt an iterative multi-scale, systems biology approach coupled to in vitro experimentation to investigate the roles of sugar and fat metabolism in NAFLD pathogenesis. The use of fructose as a sweetening agent is controversial; to explore this, we developed a predictive model of human monosaccharide transport, signalling and metabolism. The resulting quantitative model comprising a kinetic model describing monosaccharide transport and insulin signalling integrated with a hepatocyte-specific genome-scale metabolic network (GSMN). Differential kinetics for the utilisation of glucose and fructose were predicted, but the resultant triacylglycerol production was predicted to be similar for monosaccharides; these predictions were verified by in vitro data. The role of physiological adaptation to lipid overload was explored through the comprehensive reconstruction of the peroxisome proliferator activated receptor alpha (PPARα) regulome integrated with a hepatocyte-specific GSMN. The resulting qualitative model reproduced metabolic responses to increased fatty acid levels and mimicked lipid loading in vitro. The model predicted that activation of PPARα by lipids produces a biphasic response, which initially exacerbates steatosis. Our data support the evidence that it is the quantity of sugar rather than the type that is critical in driving the steatotic response. Furthermore, we predict PPARα-mediated adaptations to hepatic lipid overload, shedding light on potential challenges for the use of PPARα agonists to treat NAFLD

Whole genome sequencing to evaluate the resistance landscape following antimalarial treatment failure with fosmidomycin-clindamycin

Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days post treatment with a fosmidomycin-clindamycin combination. However, 28-day cure rates were low (45.9%), due to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we utilized a selective whole genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pre-treatment and post-recrudescence samples were subjected to whole genome sequencing to identify nucleotide variants. We find that our data do not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we find that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies